Induction of autophagy correlates with increased parasite load of Leishmania amazonensis

详细信息    查看全文

• 作者：Roberta O. Pinheiro ; Marise P. Nunes ; Carla S. Pinheiro ; Heloí ; sa D'Avila ; Patrí ; cia T. Bozza ; Christina M. Takiya ; Suzana Cô ; rte-Real ; Cé ; lio G. Freire-de-Lima ; George A. DosReis
• 关键词：Leishmania amazonensis ; Autophagy ; Macrophage ; Prostaglandin
• 刊名：Microbes and Infection
• 出版年：2009
• 出版时间：February 2009
• 年：2009
• 卷：11
• 期：2
• 页码：181-190
• 全文大小：727 K

文摘

We investigated the role of autophagy in infection of macrophages by Leishmania amazonensis. Induction of autophagy by IFN-γ or starvation increased intracellular parasite load and the percentages of infected macrophages from BALB/c but not from C57BL/6 mice. In contrast, starvation did not affect the replication of either Leishmania major or Trypanosoma cruzi in BALB/c macrophages. In BALB/c macrophages, starvation resulted in increased monodansylcadaverine staining and in the appearance of double-membrane and myelin-like vesicles characteristic of autophagosomes. Increased parasite load was associated with a reduction in NO levels and was attenuated by wortmannin, an inhibitor of autophagy. In infected macrophages from BALB/c, but not from C57BL/6 mice, starvation increased the number of lipid bodies and the amounts of PGE₂ produced. Exogenous PGE₂ increased parasite load in macrophages from BALB/c, but not C57BL/6 mice. The cyclooxygenase inhibitor indomethacin prevented the increase of parasite load in starved BALB/c macrophages, and actually induced parasite killing. These results suggest that autophagy regulates the outcome of L. amazonensis infection in macrophages in a host strain specific manner.